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Low Grade Glioma

Low-grade gliomas (LGGs) are a diverse group of WHO grade I - WHO grade II primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course.


Low grade gliomas (LGGs) are generally located in the temporal lobe.

see Temporal lobe low grade glioma.


With the advance of genomics research, there have been a new breakthrough in the molecular classification of gliomas. Glioblastoma (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesenchymal according to the mRNA expression. Low grade gliomas (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p/19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and TERTp (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas. Genotype and phenotype were integrated to diagnose gliomas. In the meantime, precision treatment for gliomas has also been vigorously developed 1).

With the increased understanding of glioma tumour genetics there is a need to understand the changes and their implications for patient management. There has also been an increasing trend for adopting earlier, more aggressive surgical approaches to low grade glioma treatment 2).

Verma and Mehta et al., discuss the recent genomics of gliomas, and also the results of seminal LGG trials in the context of molecular and genomic stratification, with respect to both prognosis and response to therapy.

They also analyze implications of these “molecular classifications”. They propose separating out the worst prognostic subsets, whose outcomes resemble those of glioblastoma patients. Lastly, a brief discussion is provided regarding translating this collective knowledge into the clinic and in treatment decisions; also addressed are some of the many questions that still need to be examined in light of these strong and emerging data 3).

High risk low grade glioma

By age

Pediatric low grade glioma….

By localization

Low grade midbrain glioma


They include a number of subtypes:

fibrillary astrocytoma

protoplasmic astrocytoma

gemistocytic astrocytoma

and mixed tumours, e.g. oligoastrocytoma

The term should not be used for a specific, non-infiltrative WHO I tumour of astrocyte-lineage such as pleomorphic xanthoastrocytoma (PXA), subependymal giant cell astrocytoma (SGCA) and pilocytic astrocytoma, as these have different prognosis, treatment and imaging features.

Molecular profile

The most critical molecular alterations (IDH1/2, 1p/19q codeletion, ATRX, TERT, CIC, and FUBP1) and circumscribed (BRAF-KIAA1549, BRAF(V600E), and C11orf95-RELA fusion) gliomas. These molecular features reflect tumor heterogeneity and have specific associations with patient outcome that determine appropriate patient management. This has led to an important, fundamental shift toward developing a molecular classification of World Health Organization grade II-III diffuse glioma 4)

Clinical features

Preoperative seizures could reflect intrinsic glioma properties 5).

Most patients experience epileptic seizures as a presenting symptom 6) 7) 8) 9) and cause medically-intractable seizure.

see Incidental low grade glioma.

The results of a genomic analysis suggest that low FOXO4 expression is a significant risk factor for epileptic seizures in patients with LGGs and is associated with the seizure outcome. FOXO4 may be a potential therapeutic target for tumor-associated epilepsy 10).

In patients with low-grade glioma (LGG), language deficits are usually only found and investigated after surgery. Deficits may be present before surgery but to date, studies have yielded varying results regarding the extent of this problem and in what language domains deficits may occur.

Twenty-three patients were tested using a comprehensive test battery that consisted of standard aphasia tests and tests of lexical retrieval and high-level language functions. The patients were also asked whether they had noticed any change in their use of language or ability to communicate. The test scores were compared to a matched reference group and to clinical norms. The presumed LGG group performed significantly worse than the reference group on two tests of lexical retrieval. Since five patients after surgery were discovered to have a high-grade glioma, a separate analysis excluding them were performed. These analyses revealed comparable results; however one test of word fluency was no longer significant. Individually, the majority exhibited normal or nearly normal language ability and only a few reported subjective changes in language or ability to communicate. This study shows that patients who have been diagnosed with LGG generally show mild or no language deficits on either objective or subjective assessment 11).


Arterial spin labelled imaging, DTI, and Proton magnetic resonance spectroscopic imaging are useful for predicting glioma grade. Additionally, the parameters obtained on DTI and MR spectroscopy closely correlated with the proliferative potential of gliomas 12).

The Apparent Diffusion Coefficient (ADC) values of low-grade (WHO I-II) glioma were higher than that of high-grade (WHO III-IV), but the cell density of low-grade glioma was apparently lower than that of high-grade glioma. The ADC values and density of tumor cells were negatively correlated with WHO malignant grades, while the density of cells of glioma was positively correlated with WHO malignant grades 13).

Usually, low grade gliomas show no increase in tumor rCBV, whereas high grade gliomas demonstrate high relative cerebral blood volume (rCBV) that in some cases even extends outside the contrast-enhancing portions of the tumor 14).

Preoperative rCBV is one of the important prognostic factors significantly connected with survival 15).



Case series

A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and field-strength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment.

A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas “failed” GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio: 2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio: 0.51, P < .01) was positively and eloquent location (odds ratio: 1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits.

GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS 16).

Hua W, Mao Y. [Advance of molecular subtyping and precise treatment for gliomas]. Zhonghua Wai Ke Za Zhi. 2017 Jan 1;55(1):63-66. doi: 10.3760/cma.j.issn.0529-5815.2017.01.016. Chinese. PubMed PMID: 28056258.
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Verma V, Mehta MP. Clinical ramifications of “genomic staging” of low-grade gliomas. J Neurooncol. 2016 Sep;129(2):195-9. doi: 10.1007/s11060-016-2192-z. Review. PubMed PMID: 27401152.
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Smits A, Duffau H. Seizures and the natural history of World Health Organization grade II gliomas: a review. Neurosurgery. 2011;68:1326–1333.
Liigant A, Haldre S, Oun A, et al. Seizure disorders in patients with brain tumors. Eur Neurol. 2001;45:46–51.
Lynam LM, Lyons MK, Drazkowski JF, et al. Frequency of seizures in patients with newly diagnosed brain tumors: a retrospective review. Clin Neurol Neurosurg. 2007;109:634–638.
Rosati A, Tomassini A, Pollo B, et al. Epilepsy in cerebral glioma: timing of appearance and histological correlations. J Neurooncol. 2009;93:395–400.
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Wang Y, Tang K, Zhao J, Liu L, Feng J. FOXO4 expression is associated with the occurrence and outcome of seizures: An RNA-sequencing analysis of low-grade gliomas. Seizure. 2017 Sep 21;52:41-45. doi: 10.1016/j.seizure.2017.09.012. [Epub ahead of print] PubMed PMID: 28963932.
Antonsson M, Longoni F, Jakola A, Tisell M, Thordstein M, Hartelius L. Pre-operative language ability in patients with presumed low-grade glioma. J Neurooncol. 2017 Dec 1. doi: 10.1007/s11060-017-2699-y. [Epub ahead of print] PubMed PMID: 29196925.
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low_grade_glioma.txt · Last modified: 2017/12/05 08:20 by administrador